Sofosbuvir and velpatasvir for HCV Genotype 2 and 3 infection

G. R. Foster, N. Afdhal, S. K. Roberts, N. Br, E. J. Gane, S. Pianko, E. Lawitz, A. Thompson, M. L. Shiffman, C. Cooper, W. J. Towner, B. Conway, P. Ruane, M. Bourlie, T. Asselah, T. Berg, S. Zeuzem, W. Rosenberg, K. Agarwal, C. A.M. StedmanH. Mo, H. Dvory Sobol, L. Han, J. Wang, J. McNally, A. Osinusi, D. M. Brainard, J. G. McHutchison, F. Mazzotta, T. T. Tran, S. C. Gordon, K. Patel, N. Reau, A. Mangia, M. Sulkowski

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Abstract

BACKGROUND In phase 2 trials, treatment with the combination of the nucleotide polymerase inhibitor sofosbuvir and the NS5A inhibitor velpatasvir resulted in high rates of sustained virologic response in patients chronically infected with hepatitis C virus (HCV) genotype 2 or 3. METHODS We conducted two randomized, phase 3, open-label studies involving patients who had received previous treatment for HCV genotype 2 or 3 and those who had not received such treatment, including patients with compensated cirrhosis. In one trial, patients with HCV genotype 2 were randomly assigned in a 1:1 ratio to receive sofosbuvir-velpatasvir, in a once-daily, fixed-dose combination tablet (134 patients), or sofosbuvir plus weight-based ribavirin (132 patients) for 12 weeks. In a second trial, patients with HCV genotype 3 were randomly assigned in a 1:1 ratio to receive sofosbuvir-velpatasvir for 12 weeks (277 patients) or sofosbuvir-ribavirin for 24 weeks (275 patients). The primary end point for the two trials was a sustained virologic response at 12 weeks after the end of therapy. RESULTS Among patients with HCV genotype 2, the rate of sustained virologic response in the sofosbuvir-velpatasvir group was 99% (95% confidence interval [CI], 96 to 100), which was superior to the rate of 94% (95% CI, 88 to 97) in the sofosbuvir-ribavirin group (P = 0.02). Among patients with HCV genotype 3, the rate of sustained virologic response in the sofosbuvir-velpatasvir group was 95% (95% CI, 92 to 98), which was superior to the rate of 80% (95% CI, 75 to 85) in the sofosbuvir-ribavirin group (P<0.001). The most common adverse events in the two studies were fatigue, headache, nausea, and insomnia. CONCLUSIONS Among patients with HCV genotype 2 or 3 with or without previous treatment, including those with compensated cirrhosis, 12 weeks of treatment with sofosbuvir- velpatasvir resulted in rates of sustained virologic response that were superior to those with standard treatment with sofosbuvir-ribavirin. (Funded by Gilead Sciences; ASTRAL-2 ClinicalTrials.gov number, NCT02220998; and ASTRAL-3, NCT02201953.)

Original languageEnglish (US)
Pages (from-to)2608-2617
Number of pages10
JournalNew England Journal of Medicine
Volume373
Issue number27
DOIs
StatePublished - Dec 31 2015
Externally publishedYes

ASJC Scopus subject areas

  • General Medicine

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